The Galpha12/13 subfamily of G-protein coupled receptors activates Rho and Rho-dependent cellular processes, including cytoskeletal rearrangement, and serum response element (SRE)-dependent gene transcription. The RGS domain containing rhoGEF, LARG (leukemia-associated rhoGEF), and the actin- regulated transcritpional SRF-coactivator MAL (modified in acute leukemia) are purtative oncogenes involved in the Galpha12/13 and Rho mediated SRE-depenedent gene transcription. These molecules and their signaling pathway are potentially important in cancer and cancer metastasis. Thus, I plan to utilize a high-throughput screening approach to develop a chemical inhibitor of these molecules or other molecules in their signaling pathway. Inhibitors identified in the high throughput screen will be mechanistically characterized to define their specific molecular target. Such inhibitors should provide useful scientific tools to better understand the role of rho-mediated transcriptional signaling pathways in cancer metastasis.